Previous studies suggest that NGAL (neutro phil gelatinase-associated lipocalin) is involved in the transformation and development of esophageal carcinoma. Alteration of NGAL expression can trigger the change of cellular morphology in esophageal carcinoma cells. However, the mechanisms remain unclear. To get a better understanding of NGAL function in esophageal carcinoma, NGAL protein was expressed in methylotrophic yeast, Pichia pastoris, and purified by chromatography. EC1.71 cells expressed high levels of NGALR (NGAL receptor) and EC109 cells expressed low levels of NGALR were used as cells model. The trafficking and the possible function of NGAL protein were then analyzed in the esophageal carcinoma cells. The results showed that 5-FAM-labeled recombinant NGAL protein could internalize into the EC1.71 and EC109 cells. Furthermore, the internalized NGAL protein could induce the alteration of cellular morphology, resulting in generation of autophagosome, transcriptional up-regulation of genes associated with autophagy and increase of phospho-ERK1/2 (p-ERK1/2). Interestingly, the treatment with the NGAL protein did not affect the intracellular iron level. These data indicate that induced autophagy by exogenous NGAL protein is a mechanism that internalized NGAL plays important roles in esophageal carcinoma cells, independent with NGAL-mediated iron transport process, while ERK1/2 signal pathway is involved in activation of autophagy by exogenous NGAL protein.

Objective To study the effects of ionic and group Ⅰ metabotropic glutamate receptors on rats' thermal hypersensitivity by intraplantar administration of drugs. Methods After intraplantar administration of glutamate receptor agonists,L-glutamic acid (Glu), N-methyl-D-aspartic-acid (NMDA),and (RS)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid hydrobromide (AMPA);a Group Ⅰ mGluR agonist, (S) 3,5-dihydroxyphenylglycine [(S)-DHPG];a noncompetitive NMDA receptor antagonist, (+)-MK801 maleate (MK-801);a competitive AMPA/kainate receptor antagonist,6-cyano-7-nitroquinoxaline-2,3-dione (CNQX);and a selective GroupⅠ mGluR antagonist,7-hydroxyiminocyclo propan[b]chromen-1a- carboxylic acid ethyl ester (cpccoEt) into the left hind paws of rats whose L5-6 nerves were sham-operated or ligated,we examined the response of the rats to thermal stimuli provided by radiant heat. Results In sham-operated rats,glutamate,NMDA,AMPA,and (S)-DHPG reduced paw withdrawal latency (PWL) but did not have any effect on SNL rats. However,in SNL rats,MK-801,CNQX,and cpccoEt increased PWL but exerted no effect on sham-operated rats. Conclusion These results suggest that changes in sensitivity of peripheral ionic and group Ⅰ metabotropic glutamate receptors can lead to changes in peripheral nerve plasticity;the generation and maintenance of neuropathic pain caused by nerve injury is based on this plasticity.

Objective: To analyze the clinical characteristics of X-linked inhibitor of apoptosis (XIAP) deficient patients with clinical manifestation of Crohn's disease. Methods: Clinical manifestations, laboratory investigations, genetic testing and therapeutic interventions of one case of XIAP deficiency who was admitted to Department of Gastroenterology in Children's Hospital, Zhejiang University School of Medicine in May 2016 were summarized. PubMed and Chinese database for articles published from January 2016 to June 2017 were searched using the key words of'Crohn's disease’and'XIAP’, and the relevant literature was reviewed. Results: The case we reported was a 6-year-1-month-old boy with recurrent bloody stool for 2 months, and abdominal pain with fever for 2 weeks. The patient had a past history of hemophagocytic lymphohistiocytosis (HLH) and epilepsy in the past one year. Complete blood cell count showed mild anemia (Hb108 g/L). The patient had an elevated high-sensitivity C reactive protein (86 mg/L) and erythrocyte sedimentation rate (46 mm/1h) . White blood cells, pus cells and red blood cells were found on routine stool examination. Biochemical panel showed hypoalbuminemia (25.2 g/L) , elevated transaminase (alanine aminotransferase 175 U/L, aspartate transaminase 229 U/L) , hypertriglyceridemia (4.41 mmol/L) , and hyperferritinemia (>1 650.0 μg/L) . Magnetic resonance enterography revealed the intestinal wall thickening and increased enhancement in parts of illeum and colon. Capsule endoscopy revealed multiple ulcers in jejunum. Colonoscopy showed multiple ulcers in colon and the pathological examination revealed chronic inflammation in mucosa of terminal ileum and colon, which was combined with partial necrosis and ulceration. Some phagocytes were seen in bone marrow smears. The patient was given multiple diagnoses, including hemophagocytic lymphohistiocytosis, Crohn's disease, sepsis, epilepsy, severe malnutrition, and hypoproteinemia. The pediatric Crohn's disease activity index (PCDAI) was 37.5. Genetic testing identified a hemizygotic mutation of c.910G>T chrX:123022501 p.G304X in XIAP. The parents had no such mutation. The patient showed response to infliximab with oral intake of mercaptopurine and corticosteroids, and had remission with PCDAI of 0. There were 9 relevant articles (Chinese 0 English 9), which showed 33.3% XIAP deficient patients manifested with inflammatory bowel disease(IBD), who might have other manifestations such as hemophagocytic lymphohistiocytosis or splenomegaly simultaneously or sequentially. Those patients showed poor response to monotherapy. Conclusion XIAP deficient patients have various clinical manifestations. Genetic testing is important to those male pediatric IBD patients who have the complicated symptoms or little response to standard therapy.

Objective To explore the efficacy and safety of the application of enteral nutrition (EN) in gastrointestinal disease in children,and to explore the possibility of the implementation of family EN.Method Retrospective analysis of disease spectrum,EN approach,preparation,speed and time as well as adverse reactions and outcomes in 47 pediatric patients with gastrointestinal disease underwent EN therapy during July 2014 to March 2015.The nutrition indicators before and after EN therapy were compared by paired t-test.Result A total of 47 patients were selected,27 male (57％) and 20 female (43％),aged 0.8 (0.3,4.0) years,9 with mechanical or chemical damage to the esophagus,7 with inflammatory bowel disease (including ulcerative colitis and Crohn's disease),6 with chronic diarrhea,5 with acute pancreatitis,3 with acute diarrhea and severe malnutrition,3 with short bowel syndrome,3 with improper feeding,3 with feeding difficulties,3 with protein losing enteropathy,2 with post-enterostomy,2 with enterocolitis,1 with gastroesophageal reflux,were diagnosed.Of 47 cases,22 were given oral nutrition,28 were fed with nasogastric tube and 4 with nasojejunal tube feeding,2 with percutaneous endoscopic gastrojejunostomy tube feeding for each.In these tube-feeding cases,20 cases were treated with continuous infusion and 21 cases with intermittent infusion.Eleven cases were fed with amino acid formula;21 cases took the choice of peptide formulations;16 cases chose whole protein formula,including six cases who chose 3.3-4.2 kJ/ml higher energy density formula,10 cases selected common energy density formula including breast milk.Twenty-one cases suffered from different degrees of adverse reactions,including vomiting in 7 cases,abdominal pain and bloating in 3,diarrhea in 12,secondary respiratory infections in 5.Five patients were discharged after giving up of treatment by parents due to poor efficacy on primary disease;3 cases were transferred to other departments for further treatment;15 cases were discharged with a feeding tube for family nutrition and specialist out-patient treatment.The rest 24 cases were all improved and discharged.There were significant differences in nutrition indicators before and after EN,weight-for-age Z score (WAZ)(-2.3 ± 1.9 vs.-1.9 ± 1.8,t =4.156,P =0.000),weight-for-height Z score (WHZ) (-1.9 ± 1.7 vs.-1.2±1.5,t=3.714,P=0.001),albumin ((35 ±9)g/L vs.(39 ±6) g/L,t=3.017,P=0.005) and prealbumin ((0.11 ±0.05)g/L vs.(0.18 ±0.07)g/L,t=5.144,P=0.000).Conclusion EN is suitable for a variety of children's digestive diseases,which can improve the nutritional status of the patients and was safe for clinical application.As the implementation of EN is simple and has good compliance,family EN is proven to be feasible.

Objective: To explore the clinical features and complications of foreign bodies in the upper gastrointestinal tract in children and to investigate the effectiveness of endoscopic management. Methods: Data of patients with foreign bodies in upper gastrointestinal tract were collected retrospectively at Endoscopy Center, the Children's Hospital, Zhejiang University School of Medicine, from January 2011 to December 2016. Clinical characteristics, the types of foreign bodies, the location and duration of foreign body impaction were summarized. The risk factors of complications and endoscopic removal failure were analyzed by using Logistic regression analysis. Results: A total of 1 334 patients (825 males and 509 females) were enrolled. The median age was 2.5 years, with a range from 0.25 to 15 years and peak age 1-3 years. Twenty patients had esophageal diseases. The most common foreign body ingested was coin (n=964, 72.3%). Foreign bodies were most commonly located in the esophagus (n=1 002, 75.1%), especially in the upper esophagus (n=857, 85.5%). The duration of foreign body impaction ranged from 3 hours to 5 years. Among 1 334 patients, 252 patients (18.9%) developed complications, including ulcers (n=101, 40.0%) and perforations(n=13, 5.2%). The success rate of endoscopic removal was 96.6% (n=1 288). By Logistic regression analysis, sharp foreign body ingestion (OR=6.893, 95%CI: 4.421-10.746) , esophageal impaction (OR=5.253, 95%CI:3.352-8.233) and foreign body impaction longer than 24 hours (OR=4.336, 95%CI:3.091-6.082) were risk factors of complications. Sharp foreign body ingestion was the risk factor of endoscopic failure (OR=5.372, 95%CI:2.773-10.406) . Conclusions Coin is the most common foreign body in upper gastrointestinal tract. Sharp foreign bodies impacted in the esophagus over 24 hours increase the risk of complications. Endoscopic removal of foreign bodies from the upper gastrointestinal tract in children has a high success rate. Sharp foreign body ingestion increases the risk of failure in endoscopic removing.

Objective:To explore the incidence and the risk factors of post-polypectomy bleeding and polyp recurrence after colonoscopic high-frequency electrocoagulation snare polypectomy.Methods:Clinical data of 1 826 children who underwent colonoscopic high-frequency electrocoagulation snare polypectomy in the Children′s Hospital, Zhejiang University School of Medicine from January 2009 to December 2020 was retrospectively analyzed. Demographic characteristics, endoscopic manifestations, pathological features, diagnosis, occurrence of post-polypectomy bleeding and polyp recurrence were collected. The associated risk factors were analyzed by Logistic regression.Results:A total of 1 826 children (1 191 males and 635 females) with 1 967 polypectomies were included. The age was 4.6 (3.2, 6.4) years at initial diagnosis. According to the initial colonoscopy, 1 611 children (88.2%) had solitary polyps, 1 707 children (93.5%) had pedicled polyps, 1 151 children (63.0%) had polyps involving the rectum, and 1 757 children (96.2%) had hamartomatous polyps. Polyposis syndromes were diagnosed in 73 children (4.0%). The post-polypectomy bleeding occurrence was 3.8% (75/1 967). Polyps recurred in 88 children (4.8%). Girls ( OR=2.01, 95% CI 1.26-3.23) and sessile polyps ( OR=2.28, 95% CI 1.15-4.49) were risk factors for post-polypectomy bleeding (both P<0.05). Multiple polyps ( OR=17.49, 95% CI 9.82-31.18), right-colon involvement ( OR=3.44, 95% CI 1.89-6.26) and non-hamartoma ( OR=2.51, 95% CI 1.04-6.07) were risk factors for polyp recurrence (all P<0.05). Conclusions:Colonoscopic high-frequency electrocoagulation snare polypectomy has low incidence of post-polypectomy bleeding and polyp recurrence. Female patients and sessile polyps have higher risk for post-polypectomy bleeding. Multiple polyps, right-colon involvement and non-hamartoma polyps increase the risk for polyp recurrence.

Objective:To investigate the correlation between red cell volume distribution width (RDW) variation coefficient and mortality in patients with liver cirrhosis complicated with sepsis.Methods:From 2008 to 2019, the real clinical data of patients admitted to the intensive care unit (ICU) of Beth Israel Deaconess Medical Center, Massachusetts Institute of Technology were selected from the American Medical Information Mart for Intensive Care-Ⅳ (MIMIC-Ⅳ) database. Structured Query Language was used to extract the demographic information, physiological indicators, laboratory test indicators, complications, in-hospital mortality, and sequential organ failure assessment (SOFA) score from the MIMIC-Ⅳ database. Analysis of variance and Kruskal-Wallis test were used to analyze the characteristics of patients in different quartiles of RDW variation coefficient and the correlation between RDW variation coefficient and different outcomes. The clinical and prognostic variables were included in the logistic regression model and its adjustment models for analysis. Model 1 was adjusted according to age and gender, and model 2 was adjusted according to age, gender, SOFA score, bilirubin, albumin, body weight, white blood cell count, serum creatinine, serum sodium, dialysis treatment, and with congestive heart failure or not. A cubic spline regression model was used to analyze the dose-response relationship between RDW variation coefficient and in-hospital mortality, ICU mortality, mild to moderate disorders of consciousness in patients with liver cirrhosis complicated with sepsis. Trend tests were performed to analyze the interaction between the RDW variation coefficient and the variables used for stratification.Results:A total of 1 443 patients with liver cirrhosis complicated with sepsis were included, with a median age of 59.0 (52.0, 67.0) years old. Among them, 954 (66.1%) were male and 489 (33.9%) were female. The RDW variation coefficient was 3.49±2.50. Totally 382 patients died during hospitalization, 246 patients died in ICU, and 259 patients with mild to moderate disorders of consciousness. When RDW variation coefficient was analyzed as a continuous variable, the OR values (95% confidence interval (95% CI)) of unadjusted model, model 1, and model 2 in in-hospital mortality, ICU mortality and mild to moderate disorders of consciousness were 1.12 (1.09 to 1.16), 1.14 (1.10 to 1.17), 1.08 (1.03 to 1.13); 1.11 (1.07 to 1.15), 1.12 (1.08 to 1.16), 1.07 (1.02 to 1.12); and 1.16 (1.12 to 1.20), 1.16 (1.12 to 1.20), 1.12 (1.07 to 1.17); respectively. The fourth quartile of RDW variation coefficient (>4.74, 29.08) was taken as the control group, the OR values (95% CI) of the unadjusted model, model 1, and model 2 were 3.00 (2.13 to 4.25), 3.32 (2.34 to 4.74), 1.76 (1.10 to 2.84); 3.42 (2.27 to 5.26), 3.81 (2.50 to 5.90), 1.77 (1.03 to 3.11); and 8.52 (5.23 to 14.63), 8.35 (5.10 to 14.38), 5.56 (2.87 to 11.69); respectively. There was a linear correlation between RDW variation coefficient and in-hospital mortality, ICU mortality, mild and moderate disorders of consciousness (all P<0.05). Among patients with higher SOFA scores, along with the increase of RDW variation coefficient, the increase of in-hospital mortality, ICU mortality and the incidence of mild and moderate disorders of consciousness, were more significant than those of patients with lower SOFA scores ( P=0.022, 0.024, and 0.001). Conclusion:Variation coefficient of RDW is associated with increased risk of disorders of consciousness and in-hospital mortality in patients with liver cirrhosis complicated with sepsis.

Abstract OBJECTIVE To investigate the effect of infliximab through concentration and antibody monitoring on the clinical outcome of children with Crohn's disease after 54 weeks of treatment. METHODS A retrospective analysis was conducted with clinical data of pediatric patients aged 6-17 years who were diagnosed with Crohn's disease at Children's Hospital, Zhejiang University School of Medicine from August 2017 to March 2023. They were divided into a reactive and a proactive monitoring group according to the monitoring method. The mucosal healing rate, disease activity, and laboratory indicators were compared after 54 weeks of treatment. RESULTS There were 77 pediatric patients with Crohn's disease included, with 34 patients from the reactive therapeutic drug monitoring group and 43 from the proactive therapeutic drug monitoring group, including 48 males and 29 females. At 54 weeks, the mucosal healing rate in the proactive therapeutic drug monitoring group was higher than that in the reactive therapeutic drug monitoring group, which was 80%(24/30) and 46.43%(13/28), respectively. The two groups had a statistical difference(P=0.01). The total clinical remission rate at 54 weeks was 84.42%(65/77), while the clinical remission rates at 54 weeks were 76.47%(26/34) in the reactive therapeutic drug monitoring group and 90.70%(39/43) in the proactive therapeutic drug monitoring group, respectively. The two groups had no statistical difference. The improvement of hypersensitive C-reactive protein, erythrocyte sedimentation rate, and serum albumin level in the proactive monitoring group was greater than in the reactive monitoring group. There was no statistical difference in the production rate of antibodies to infliximab between the two groups. CONCLUSION Proactive therapeutic drug monitoring in detecting through concentration of infliximab and antibodies may improve the mucosal healing rate compared with reactive therapeutic drug monitoring after 54 weeks of infliximab treatment.